Data from Cross-resistance of Belinostat and Romidepsin in Non–T Follicular Helper Peripheral T-cell Lymphoma Models Suggests Subtype-Specific Implications for Belinostat-CHOP
Year: 2026
Type: other
Abstract: The phase III study of romidepsin plus CHOP for peripheral T-cell lymphoma (PTCL) yielded negative results in the overall analysis and showed that outcomes were only improved in the T follicular helper (TFH) subgroup of PTCL, with no benefit in non–TFH PTCL. Belinostat, another histone deacetylase (HDAC) inhibitor, is now the primary candidate to test whether HDAC inhibition can improve treatment outcomes in first-line PTCL. Whether belinostat shares romidepsin’s TFH-specific clinical activity remains uncertain, and therefore whether it is better to include or exclude non-TFH subtypes may be a crucial choice for a forthcoming confirmatory trial of belinostat-CHOP in first-line PTCL. We evaluated whether these agents are cross-resistant in non-TFH lymphomas by conducting in vitro drug sensitivity profiling with belinostat, romidepsin, and other pairs of mechanistically related agents in 30 non-TFH human T- and NK-cell lymphoma cultures. Sensitivities to romidepsin and belinostat were strongly correlated (ρ = 0.77, P < 10−6) and comparable with correlations observed for other same-mechanism drug pairs (e.g., doxorubicin/etoposide) and significantly higher than for drug pairs without mechanistic similarity. These findings indicate substantial cross-resistance between romidepsin and belinostat in non–TFH PTCL. If belinostat shares romidepsin’s subtype-specific activity, a first-line trial of belinostat plus CHOP with broad patient enrollment may risk diluting benefit in TFH lymphomas by including non-TFH cases, whereas a TFH-focused design could maximize the likelihood of the trial’s success.
Authors: Jacob C. Pantazis, Adam C. Palmer
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
OpenAlex ID: W7147060124
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